An ongoing pilot study has established the validity of a guinea pig model for studying ocular disease caused by Herpes simplex virus, type 1 (HSV-1). Under development in our laboratory is a vaccine containing primarily Alpha and Beta class HSV-1 polypeptides (early polypeptide vaccine (EPV)) which will be tested for its capacity to prevent herpetic ocular infections and viral latency in guinea pigs. This vaccine is highly protective against lethal HSV infections in mice and shows promise in preventing serious herpetic eye disease in guinea pigs. The long range objective of our research is to develop a safe and effective vaccine which may become a candidate for the protection of herpetic ocular disease in humans. Employing the guinea pig model, the specific aims of this proposal are: 1) to establish the efficacy of EPV immunization in preventing herpetic ocular infections and HSV-1 latency in trigeminal ganglia, 2) to examine the effect of EPV immunization on latently-infected animals, 3) to characterize the humoral and cell-mediated immune responses to EPV and in EPV-immunized, corneally-infected animals, and 4) attempt to define the antigenic composition of EPV and identify the HSV-1 antigens responsible for preventing ocular infections and viral latency.